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Optogenetic gene therapy aims to restore vision in affected individuals by introducing light-sensitive opsins into the surviving neurons of the inner retina. While up until now, the main focus of optogenetic therapy has been on terminally blind individuals, treating at stages where residual native vision is present could have several advantages. However, it is still unknown how residual native and optogenetic vision would interact if present at the same time. Using transgenic mice expressing the optogenetic tool ReaChR in ON-bipolar cells, we herein examine this interaction through electroretinography (ERG) and visually evoked potentials (VEP). We find that optogenetic responses show a peculiar ERG signature and are enhanced in retinas without photoreceptor loss. Conversely, native responses are dampened in the presence of ReaChR. Moreover, in VEP recordings, we find that optogenetic responses reach the cortex asynchronous to the native response. These findings should be taken into consideration when planning future clinical trials and may direct future preclinical research to optimize optogenetic approaches for visual restoration. The identified ERG signatures, moreover, may serve to track treatment efficiency in clinical trials.<\/jats:p>","DOI":"10.1172\/jci.insight.190785","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T12:00:19Z","timestamp":1744718419000},"source":"Crossref","is-referenced-by-count":7,"title":["Interaction between native and prosthetic visual responses in optogenetic visual restoration"],"prefix":"10.1172","volume":"10","author":[{"given":"Eleonora","family":"Carpentiero","sequence":"first","affiliation":[{"name":"Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Hughes","sequence":"additional","affiliation":[{"name":"The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, and"},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Rodgers","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine & Health, University of Manchester, Manchester, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermina","family":"Xhaferri","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Gilhooley","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London, United Kingdom."},{"name":"Department of Neuro-ophthalmology, University of Colorado, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Hankins","sequence":"additional","affiliation":[{"name":"The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, and"},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Lindner","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, Germany."},{"name":"The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, and"},{"name":"Department of Ophthalmology, Philipps University Marburg, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S241928"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s10198-019-01115-5"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S365486"},{"key":"B4","unstructured":"World Health Organization. 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